Abstract:
BACKGROUND:Sacituzumab govitecan (IMMU-132), an antitrophoblastic cell-surface antigen (anti-Trop-2) humanized antibody-SN-38 conjugate, had encouraging efficacy in the phase 1 clinical trial. This report further examines the pharmacokinetics and safety of multiple cycles of IMMU-132 at doses of 8 or 10 mg/kg in patients with diverse advanced epithelial cancers. METHODS:Patients who had multiple prior therapies received IMMU-132 on days 1 and 8 of 21-day treatment cycles. Trop-2 staining of archived tumor specimens, clearance of IMMU-132 and its constituents (ie, immunoglobulin G [IgG], SN-38 [a camptothecin, the active component of irinotecan], and glucuronidated SN-38 [SN-38G]), antibody responses, and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) levels were determined. Safety was assessed according to Common Terminology Criteria for Adverse Events version 4.0, and responses were assessed using Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS:Patients with diverse metastatic cancers who received IMMU-132 at 8 mg/kg (n = 81) and 10 mg/kg (n = 97) were examined. Trop-2 was positive in 93% of the available specimens. IMMU-132 cleared with a half-life of approximately 11 to 14 hours, reflecting the release of SN-38 from the conjugate; IgG cleared more slowly (half-life, approximately 103-114 hours). Most SN-38 in the serum (>95%) was bound to IgG. SN-38G concentrations were lower than SN-38 concentrations. Dose-limiting neutropenia after the first cycle was not correlated with SN-38 in serum or with UGT1A1 genotype. No antibody responses were detected. Objective responses were observed in several indications, including metastatic triple-negative breast cancer, confirming that 10 mg/kg produced an encouraging overall response. CONCLUSIONS:Sacituzumab govitecan has a predictable pharmacokinetic profile and manageable toxicity at doses of 8 and 10 mg/kg. With objective responses and a good therapeutic index at 10 mg/kg, this dose was chosen for future development. Cancer 2017;123:3843-3854. © 2017 American Cancer Society.
journal_name
Cancerjournal_title
Cancerauthors
Ocean AJ,Starodub AN,Bardia A,Vahdat LT,Isakoff SJ,Guarino M,Messersmith WA,Picozzi VJ,Mayer IA,Wegener WA,Maliakal P,Govindan SV,Sharkey RM,Goldenberg DMdoi
10.1002/cncr.30789subject
Has Abstractpub_date
2017-10-01 00:00:00pages
3843-3854issue
19eissn
0008-543Xissn
1097-0142journal_volume
123pub_type
杂志文章,多中心研究相关文献
CANCER文献大全abstract:BACKGROUND:The optimal use of radiation therapy for cancer treatment is hampered by the application of tolerance limits of normal tissues derived empirically from population averages. Such limits do not reflect the considerable differences from patient to patient in susceptibility to late radiation sequelae. Assays tha...
journal_title:Cancer
pub_type: 杂志文章,评审
doi:10.1002/(SICI)1097-0142(19960601)77:11<2379::AID-C
更新日期:1996-06-01 00:00:00
abstract:BACKGROUND:Despite known benefits to needle biopsy for suspicious breast lesions, variability in the use of this technique has been documented in practice. We sought to study the use of needle biopsy and open surgical biopsy in women with breast cancer, predictors of needle biopsy use, and the effect of biopsy choice o...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/cncr.24085
更新日期:2009-02-15 00:00:00
abstract::A case of an extramedullary intrathoracic plasmacytoma causing superior vena cava syndrome is described. Review of the literature on intrathoracic plasmacytomas and superior vena cava syndrome revealed that no similar cases have been described to date. The initial presentation, management, and response to treatment ar...
journal_title:Cancer
pub_type: 杂志文章,评审
doi:10.1002/1097-0142(19910915)68:6<1376::aid-cncr2820
更新日期:1991-09-15 00:00:00
abstract::The authors observed the clinical course of 24 women with surgically removed prolactinomas for a mean postoperative interval of 62 months. The frequency of late tumor recurrence and probable factors responsible for the recurrence were investigated. Hyperprolactinemia recurred in 4 of 13 patients with microadenomas (31...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19860615)57:12<2422::aid-cncr282
更新日期:1986-06-15 00:00:00
abstract:BACKGROUND:Quality of life (QOL) issues in patients with head and neck carcinoma are of importance beyond the incidence of these tumors because of the impact of the disease and its treatment on external appearance and function of the upper aerodigestive tract. Nasopharyngeal carcinoma (NPC) patients comprise a unique s...
journal_title:Cancer
pub_type: 杂志文章
doi:
更新日期:2002-02-15 00:00:00
abstract::A controlled trial of surgical adjuvant chemotherapy for breast cancer was carried out using 551 Japanese patients. Single or combined treatment with mitomycin C (0.2 mg/kg i.v. three times within five days postoperatively) and cyclophosphamide (100 mg postoperatively daily for four months or longer) was used after ra...
journal_title:Cancer
pub_type: 临床试验,杂志文章
doi:10.1002/1097-0142(19801201)46:11<2373::aid-cncr282
更新日期:1980-12-01 00:00:00
abstract::Seventeen cases of intranasal epithelial tumors are reviewed. Thirteen were epithelial papillomas and four were squamous cell carcinomas associated with epithelial papillomas. In two cases followed over a 10 year period, transformation from an initial papilloma into a carcinoma was demonstrated. The histopathologic ca...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(197612)38:6<2503::aid-cncr282038
更新日期:1976-12-01 00:00:00
abstract::The diagnosis of malignant melanoma is based on clinical grounds and a properly performed biopsy, preferably excision, so that the type of melanoma and the thickness can be assessed by methods described by Clark and Breslow. These facilitate clinical and pathologic staging. Excisions with conservative margins for thin...
journal_title:Cancer
pub_type: 杂志文章,评审
doi:10.1002/1097-0142(19950115)75:2+<715::aid-cncr2820
更新日期:1995-01-15 00:00:00
abstract::The diagnosis of pulmonary candidiasis can only be made with certainty when tissue invasion by the organism is demonstrated histologically. In order to ascertain whether characteristic radiographic patterns are seen in patients with pulmonary candidiasis, antemortem radiographic abnormalities were correlated with auto...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(197709)40:3<1026::aid-cncr282040
更新日期:1977-09-01 00:00:00
abstract::To evaluate the utility of nuclear morphometry as a prognostic indicator in lung cancer, 5-year follow-up information was obtained in 46 cases of surgically resected Stage I non-small cell lung cancer (NSCLC). Nuclear area, perimeter, major diameter, minor diameter, and nuclear shape factor were determined from repres...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19920515)69:10<2454::aid-cncr282
更新日期:1992-05-15 00:00:00
abstract:BACKGROUND:Bortezomib is active in heavily pretreated multiple myeloma patients; the dose-limiting toxicity is peripheral neuropathy (PN). METHODS:The authors retrospectively reviewed the incidence, severity, and risk factors for PN in 78 patients who received bortezomib. The median age was 57 years (range, 33-80 year...
journal_title:Cancer
pub_type: 临床试验,杂志文章,评审
doi:10.1002/cncr.22921
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent the development of cancer by inhibiting cyclooxygenase (COX) enzymes, which are involved in carcinogenesis. Therefore, the authors of this report examined the association between NSAID use and the risk of squamous cell carcinoma (SCC), basal cell carc...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/cncr.27406
更新日期:2012-10-01 00:00:00
abstract::The value of a 3-day Hemoccult II test in the diagnosis of colorectal disease in patients receiving anticoagulant therapy was studied. The influence of rehydration and nonrehydration of the slide was investigated, as well as the reproducibility of positive tests. Eight hundred forty-nine patients on anticoagulant ther...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19841215)54:12<3054::aid-cncr282
更新日期:1984-12-15 00:00:00
abstract::Six patients with lymphomatoid granulomatosis were studied. Two patients had eye involvement, a rare manifestation of this disease. Both had complete disappearance of disease in this area after radiation therapy. One patient presented with an autoimmune hemolytic anemia, which remitted completely with chemotherapy. Th...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19820515)49:10<2070::aid-cncr282
更新日期:1982-05-15 00:00:00
abstract:BACKGROUND:This study aimed to evaluate prevalence and risk factors for emotional and behavioral problems in dependent children of cancer patients using a multinational research design. METHODS:The sample comprised 350 ill parents, 250 healthy partners, and 352 children. Parents assessed the child's psychological func...
journal_title:Cancer
pub_type: 杂志文章,多中心研究
doi:10.1002/cncr.24449
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND:Childhood cancer survivors are at risk for cardiovascular disease (CVD) because of intensive cancer therapies often accompanied by an unhealthy lifestyle. This study was aimed at 1) describing modifiable CVD risk factors in survivors and 2) investigating the association between different aspects of physical ...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/cncr.33351
更新日期:2021-01-06 00:00:00
abstract:BACKGROUND:Increased soluble human epidermal growth factor receptor 2 (sHER2) is an indicator of a poor prognosis in HER2-positive metastatic breast cancer. In this study, the authors evaluated levels of sHER2 during treatment and at the time of disease recurrence in the adjuvant North Central Cancer Treatment Group N9...
journal_title:Cancer
pub_type: 杂志文章,随机对照试验
doi:10.1002/cncr.28130
更新日期:2013-08-01 00:00:00
abstract::Plasma carcinoembryonic antigen (CEA) levels were studied in all available members of 17 families in which a presumed sporadic retinoblastoma had occurred. In 9 of the 17 families, close relatives of the patient had elevated CEA levels in the absence of demonstrable disease; this we have termed the "CEA family syndrom...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(197603)37:3<1397::aid-cncr282037
更新日期:1976-03-01 00:00:00
abstract::Fifty-one patients with confirmed bladder cancer have enrolled in a prospective evaluation of BCG immunotherapy. Following resection of existing tumors, patients were stratified according to tumor grade and number of previous recurrences and randomly assigned to control or BCG treatment groups. Immunotherapy consisted...
journal_title:Cancer
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/1097-0142(19810701)48:1<82::aid-cncr282048
更新日期:1981-07-01 00:00:00
abstract::The present overview of advanced prostate cancer required the identification of randomized clinical trials studying the question of maximal androgen blockade versus the classic castration therapy. The heterogeneity of the trials concerned the type of castration (surgical or chemical) and the type of antiandrogen (flut...
journal_title:Cancer
pub_type: 杂志文章,评审
doi:10.1002/1097-0142(19931215)72:12+<3841::aid-cncr28
更新日期:1993-12-15 00:00:00
abstract::Biopsy specimens from 62 human single primary squamous cell carcinomas (SCC) of the head and neck were xenografted into nude mice. To evaluate the prognostic significance of successful heterotransplantation, the 62 cases were retrospectively examined for survival, adjusting for possible confounders by multivariate ana...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19900701)66:1<145::aid-cncr28206
更新日期:1990-07-01 00:00:00
abstract:BACKGROUND:Strumal carcinoids (SC) are ovarian tumors containing thyroid parenchyma admixed with carcinoid elements. Microscopically, the carcinoid component of SC usually presents a ribbon or trabecular pattern similar to the pattern exhibited by hindgut carcinoids. The authors designed an immunohistochemical study to...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19930901)72:5<1673::aid-cncr2820
更新日期:1993-09-01 00:00:00
abstract::79 patients with germinal tumors of the testes were treated at the University of Maryland Radiation Therapy Clinic between January 1, 1957 and December 31, 1973. 32 of 33 patients with stage I seminoma had disease controlled for a minimum of three years for a 96.9% 3 year disease-free determinant survival. 4 of 4 pati...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(197811)42:5<2216::aid-cncr282042
更新日期:1978-11-01 00:00:00
abstract:BACKGROUND:Despite advances in first-line therapy, there are few data on treatment of glioblastoma multiforme (GBM) at recurrence. Temozolomide (TMZ) is well tolerated and may have activity despite prior TMZ exposure if novel dose schedules are used. METHODS:The authors reviewed their experience with a continuous TMZ ...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/cncr.23813
更新日期:2008-10-15 00:00:00
abstract:BACKGROUND:Introduction of human papillomavirus (HPV) vaccination for adolescent girls is being considered in the Punjab state of India. However, evidence regarding cost-effectiveness is sought by policy makers when making this decision. The current study was undertaken to evaluate the incremental cost per quality-adju...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/cncr.30734
更新日期:2017-09-01 00:00:00
abstract::Two published cases of medulloepithelioma, a rare malignant pediatric brain tumor composed of a mixture of primitive neuroepithelium and its differentiated neuronal and glial descendants, were examined by immunohistochemical staining for the presence of growth factors. From a panel of antibodies, those identifying bas...
journal_title:Cancer
pub_type: 杂志文章,评审
doi:10.1002/1097-0142(19910815)68:4<798::aid-cncr28206
更新日期:1991-08-15 00:00:00
abstract:BACKGROUND:The clinical value of DNA flow cytometry of colorectal cancer is unclear. The purpose of this retrospective study was to evaluate the relationship between tumor flow cytometry, histopathologic parameters, and survival. METHODS:Flow cytometry was performed on paraffin embedded specimens from 653 patients who...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/1097-0142(19951115)76:10<1724::aid-cncr282
更新日期:1995-11-15 00:00:00
abstract:BACKGROUND:Initial clinic studies revealed that the overexpression of proline-directed protein kinase F(A) (PDPK F(A)) is associated conversely with various stages of tumor tissue differentiation. However, the role of overexpressed PDPK F(A) in tumor cell differentiation remains unknown and needs to be established. In ...
journal_title:Cancer
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract:BACKGROUND:There is global variation in the onset of hepatocellular carcinoma (HCC). The objective of the current study was to investigate the impact of country of birth on age at the time of HCC diagnosis in the United States. METHODS:Incident HCC cases diagnosed between 2000 and 2012 in the Surveillance, Epidemiolog...
journal_title:Cancer
pub_type: 杂志文章
doi:10.1002/cncr.30246
更新日期:2017-01-01 00:00:00
abstract::The current results of trials testing combined surgery and chemotherapy in patients with breast cancer is reviewed. Information concerning eight trials utilizing nine single-agent regimens was obtained. The results at this time are conflicting. There appear to be differences among the regimens utilized in the various ...
journal_title:Cancer
pub_type: 杂志文章,评审
doi:10.1002/1097-0142(197509)36:3<881::aid-cncr2820360
更新日期:1975-09-01 00:00:00